Metastatic colonization by circulating tumour cells

Massagué, Joan; Obenauf, Anna C.

doi:10.1038/nature17038

Cited by 1,523 publications

(1,378 citation statements)

References 144 publications

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“…The migration of cancer cells was a predominant element leading to cancer recurrence 20. Compared with the saline group, CLG, Taxol (free drug formulation), and naked let‐7a did not suppress cell migration (Figure 4C,D).…”

Section: Resultsmentioning

confidence: 92%

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Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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Efficient microRNAs (miRNA) delivery into cells is a promising strategy for disease therapy, but is a major challenge because the available conventional nonviral vectors have significant drawbacks. In particular, after these vectors are entrapped in lysosomes, the escape efficiency of genes from lysosomes into the cytosol is less than 2%. Here, a novel approach for lethal‐7a (let‐7a) replacement therapy using rod‐shaped active pure drug nanoparticles (≈130 nm in length, PNPs) with a dramatically high drug‐loading of ≈300% as vectors is reported. Importantly, unlike other vectors, the developed PNPs/let‐7a complexes (≈178 nm, CNPs) can enter cells and bypass the lysosomal route to localize to the cytosol, achieving efficient intracellular delivery of let‐7a and a 50% reduction in expression of the target protein (KRAS). Also, CNPs prolong the t 1/2 of blood circulation by ≈threefold and increase tumor accumulation by ≈1.5–2‐fold, resulting in significantly improved antitumor efficacies. Additionally, no damage to normal organs is observed following systemic injection of CNPs. In conclusion, rod‐shaped active PNPs enable efficient and safe delivery of miRNA with synergistic treatment for disease. This nanoplatform would also offer a viable strategy for the potent delivery of proteins and peptides in vitro and in vivo.

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Section: Resultsmentioning

confidence: 92%

“…The 4T1 tumor is a highly metastasis breast cancer, predominantly metastasizing to the lung and secondarily to the liver 20, 23. Accordingly, metastasis of 4T1 tumor to lung in 4T1 tumor‐bearing BALB/c mice was investigated at day 16 postadministration.…”

Section: Resultsmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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“…EMT is first observed during embryogenesis in the developing fetus, but is also present during wound healing, tumor progression and tumor invasion. [29][30][31][32][33] In thyroid tumors, EMT has been linked to papillary thyroid carcinoma (PTC) progression with overexpression of vimentin and has been associated with invasion and lymph node metastasis. 34 EMT has been associated with dedifferentiated cancers such as anaplastic thyroid carcinomas (ATCs) with decreased expression of E-cadherin and membranous β-catenin and increased expression of Slug and Twist1.…”

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confidence: 99%

“…34 EMT has been associated with dedifferentiated cancers such as anaplastic thyroid carcinomas (ATCs) with decreased expression of E-cadherin and membranous β-catenin and increased expression of Slug and Twist1. [29][30][31][32][33] Using a breast cancer model, Mani et al 23 showed that acquisition of mesenchymal traits was linked to the acquisition of stem cell markers. They further showed that transformed mammary epithelial cells that had undergone EMT formed spheres, soft agar colonies and formed in vivo tumors more efficiently suggesting that the EMT program that enabled cancer cells to spread from a primary tumor may also promote their self-renewal properties.…”

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confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

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The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

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“…Metastatic tumors often respond poorly to standard therapies, underscoring the need for new and effective drugs targeting metastasis [1]. Several factors are thought to determine the survival and growth of disseminated cancer cells in a distant microenvironment.…”

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confidence: 99%